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MDTI Memorization > MDTI Memorization > Flashcards

MDTI Memorization Flashcards

1
Q

TNF alpha functions - macrophages

A

increased cytokine expression

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2
Q

TNF alpha functions - hepatocytes

A

Increased CRP expression

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3
Q

TNF alpha functions - endothelial cells

A

increased adhesion, and increase in VEGF (angiogenesis)

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4
Q

TNF alpha functions - synovial cells

A

increased MMP expression, cartilage damage

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5
Q

HLA-B27

A

MHC Class I molecule associated with SpA

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6
Q

HLA-DR4

A

MHC Class II molecule associated with Rheumatoid Athritis and “the shared epitope”

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7
Q

Abatacept

A

Drug designed to target CD80/CD86 on APC to prevent binding to CD28 on T cells (costimulation signal)

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8
Q

t(9;22)

A

Philadelphia Chromosome, CML, BCR-ABL

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9
Q

Probenecid

A

drug used for gout, inhibits URAT1, prevents reabsorption into tubule

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10
Q

Volume of Distribution

A

bioavailable dose/concentration in plama at t=0, >0.6 kg/L is distributed throughout body, <0.04 kg/L is only in plasma compartment

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11
Q

CYP3A4 Activators

A

St. John’s Wart and Rifampin, concerned about lower effective dose

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12
Q

CYP3A4 Inhibitors

A

Grapefruit and calcium channel blockers, concerned about increased effective dose and toxicity

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13
Q

Drugs that follow zero order kinetics

A

Alcohol, aspirin, phenytoin

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14
Q

Factors Affecting Drug Disposition in Neonates

A

higher volume of distribution for water soluble drugs, lower ability to extrete drugs, lower oxidative capacity, imcomplete blood brain barrier

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15
Q

Factors Affecting Drug Disposition in Elderly

A

higher volume of distribution for fat soluble drugs, lower GFR and secretion, lower oxidative capacity

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16
Q

PGF-2alpha

A

prostaglandin expressed in the uterus and vasculature, by both Cox 1 and Cox 2 causing uterine contraction and vasoconstriction

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17
Q

Carbaprost

A

PGF-2alpha analogue that is used as an abortifacient

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18
Q

Misoprost

A

PGE1 analogue that is used as an abortifacient and for its GI cytoprotective properties

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19
Q

Steroids MOA

A

Steroid receptor sits in nucleus, complexed to 2 Hsp90 proteins and 1 Hsp56 subunit. Steroid traverses plasma membrane (lipophilic) binds receptor at LBD, Hsp proteins dissociate. Steroid-receptor complex translocate into nucleus, DNA binding domain of GR binds GRE (DNA promoter). AF2 binds corepressor or coactivator and induces effector function. (AF1 is ligand independent) ex. steroids can upregulate lipocortin which downregulates expression of PLA2 which is responsible for mediating AA dissociation from plasma membrane, steroids can also downregulate expression of cytokines like IL6 and IL8

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20
Q

Methotrexate

A

inhibits DHFR, prevents DNA synthesis, cells arrest in S phase, prevents B and T cell clonal expansion, used to treat cancer and RA, side effects include anemia, leukopenia, liver dysfunction

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21
Q

Axathioprine (Imuran)

A

prevents denovo purine synthesis, prevents B and T celll clonal expansion, used to treat cancer, side effects include anemia, leukopenia, thrombocytopenia,

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22
Q

Mycophenolate (MPA) (Cellcept)

A

prevents denovo purine synthesis and the salvage pathway, prevents B and T celll clonal expansion, used to treat cancer, side effects include anemia, leukopenia, thrombocytopenia,

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23
Q

Sirolimus and Evrolimus

A

prevents mTOR signaling, prevents T cell activation and proliferation, side effects include CYP3A4 related toxicity, anemia, leukopenia, thrombocytopenia

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24
Q

Calcineurin Inhibitors (Cyclosporine and Tacrolimus)

A

NFAT inhibitor, prevents transloaciton into nucleus, prevents T cell gene expression and response to IL2 signalling, toxicity includes nephrotoxicity and hirsutism, uses the CYP3A4 pathway

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25
Q

Polyclonal Antibodies (anti-thymocyte globulin)

A

broad based antibody to B and T cells, rabbit or equine in origin, depletes circulating lymphocytes and prevents T cell function, toxicity includes antibody response (serum sickness: fever chills pruritis) and severe immunosuppression

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26
Q

Basiliximab

A

Prevents signal 3 by blocking CD25, IL2 receptor, on T cells, prevents T cell proliferation, toxicity includes anemia and leukpenia

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27
Q

Betalacept

A

Drug designed to target CD80/CD86 on APC to prevent binding to CD28 on T cells (costimulation signal), increased risk of PTLD (post-transplant lymphoproliferative disorder), edema and HTN

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28
Q

TxA2

A

prostaglandin expressed in platelets, mostly by COX1, encourages platelet aggregation and vasoconstriction

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29
Q

PGI2

A

prostaglanding expressed in vasculature, mostly by Cox2, inhibits platelet aggregation and vasoconstriction

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30
Q

PGE1 and PGE2

A

prostaglandin expressed in GI tract (cox 1 - increases gastric pH and mucus production), uterus and renal (both- uterine contraction and Na homeostasis) and diffusely (cox 2 - oncogenesis and inflammation)

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31
Q

Volume of plasma compartment

A

4L

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32
Q

Volume of ECF Compartment

A

14 L (plama plus interstitial fluid)

33
Q

Volume of total body water

A

42 L (ECF plus intercellular fluid)

34
Q

NHL vs HL

A

HL - almost always B cell NHL can be either, HL is 75% curable, NHL is 50% curable, HL has Reed Sternberg Cells, NHL has various hallmarks, HL has bimodal age curve, NHL increases with age, HL is unicentric with predictable spread, NHL is multifocal with unpredictable spread

35
Q

cisplatin

A

Causes DNA aggregation and adducts

36
Q

PLA2

A

phospholipid A 2 - promotes arachadonic acid dissociation from plasma membrane, promoting prostaglandin synthesis

37
Q

Cyclophosphamide and Ifosfamide

A

mustard derivative, progdrugs that methylate and alkylate DNA

38
Q

Doxorubicin

A

Topo II inhibitor, prevents DNA unwinding

39
Q

Topotecan and Irinotecan

A

Topo I inhibitor, prevents DNA repair of single strand breaks,

40
Q

5-Fluorouracil (5-FU)

A

interferes with enzyme uridine in thymidine synthesis, causes cell cycle arrest

41
Q

Paclitaxel (taxane)

A

Promotes microtubule stability, prevents sister chromatids from separating

42
Q

Vincas, colchicine

A

promotes microtubule instability, prevents alignment of sister chromatids

43
Q

Bevacizumab (avastin)

A

blocks VEGF binding and takes it out of circulation, used for breast cancer but not proven to do anything except improve progression free survival, in addition may promote more aggressive cancers

44
Q

Imatinab

A

blocks ATP binding site of tyrosine kinase constituitively active in CML t(9;22) philadelphia chromosome

45
Q

Erlotinib

A

blocks EGFR receptor kinase - induces cell cycle arrest

46
Q

Trastuzumab

A

targets EGFR receptor (HER-2) that is overexpressed in breast cancers, prevents ligand binding to Her-2 in breast cancer

47
Q

CML

A

chronic myeloid leukemia, can develop into AML, three stages chronic –> accelerated –> blast (like AML), 100% of the time caused by philadelphia chromosome, can be controlled lifelong with Gleevec, the following are methods of tracking the disease from least sensitive to most sensitive: WBC count, karyotyping, FISH, PCR, presents with lots of lymphocytes of varying maturity in bone marrow, small hypolobated megakaryocytes

48
Q

Polycythemia Vera

A

a myeloproliferative disorder, a clonal expansion of RBCs, high RBC mass, high hematocrit, due to JAK2 translocation causing constituively active EPO receptor, associated with low EPO signal, predisposed to develop AML

49
Q

Follicular Lymphoma

A

presents with generalized LAD, BM involvement common, paratrabecular aggregates, presents in nodular pattern in lymph node with back to back follicles, markers: CD19+CD20+CD10+BCL6+BCL2+, often due to T(14;18) translocation of IgH with BCL2, germinal center B cells that express anti-apoptotic signal, morphologically can look for cleaved cells (centrocytes), centroblasts are signs of a more aggressive disease, can transform into DLBCL

50
Q

CLL/SLL

A

interstitial bone marrow presence, diffuse monotonous appearance in lymphnodes, markers: CD19+ CD20+ CD10- CD5+, benign B cells attack RBCs and platelets resulting in anemia and microhemolytic anemia, presents with RBCs with spherocytes, smudge cells, can transform into DLBCL, two types of disease ZAP70+, unhypermutated and more agressive and ZAP70- hypermutated and more indolent

51
Q

MALT

A

cancer often presents in mucosal site, marginal B cells, expansion of marginal zone, markers: CD19+ CD20+ CD10- Bcl2+, often a result of chronic inflammation from infectious or autoimmune disease, in the beginning, the clonal hyperplasia is stimulus driven and can be treated with antibiotics, when translocation occurs t(11;18), the disease has progressed, can transform to DLBCL, disease is a result of abnormal NFkB activation

52
Q

Multiple Myeloma

A

cancer of mature B cells, presents with large presence of immunoglobulin (paraprotein), lives in bone marrow and lymph nodes, see bone pain, osteolytic lesions and pathological fractures, hypercalcemia is present, two leading causes of death include renal failure (due to immune complex deposition) and immunodeficiency, anemia due to marrow replacement and renal failure (low EPO signal), markers: CD19+ CD20+ CD56+ CD138+, serum is hyperviscious with a bluish smear, associated with bleeding, raynauds and amyloidosis

53
Q

Diffuse Large B Cell Lymphoma

A

can arise de novo or transformed from a more indolent lymphoma, diffuse presentation with presence of large transformed B cells, presents with nodal or extranodal sites, cancer is fast growing and symptomatic, see CD19+ CD20+ and Ki67+ (but not 100%), two types: germinal B cell, less agressive, and activated b cell, more aggressive

54
Q

Burkitts Lymphoma

A

3 types: endemic, sporadic and immunodef, all associated with varying populations and involvement of EBV as well as localization, very aggressive cancer with high doubling rate, cells are 100% ki67+, associated with t(8;14) which is a c-myc translocation, EBV driven B cells are allowed to proliferate due to defective T cell function, markers: CD19+ CD20+ CD10+ BCl6+

55
Q

Paroxysmal Noctrunal Hemoglobinuria (PNH)

A

Intravascular Hemolytic anemia due to mutation in PIG-4 gene which synthesizes GIP protein that protects RBC from inappropriate complement activation on its surface, RBCs sensitive to complement mediated lysis, treated with eculizumab which is a complement inhibitor

56
Q

APL

A

a particular type of AML with a t(15;17) translocation that results in a PML-RARalpha fusion protein that prevents normal function of RAR protein and prevents lymphocyte differentiation, treatment with all-trans retanoic acid (ATRA) results in differentiation

57
Q

Rivaroxiban/Apixaban

A

direct Xa inhibitor, given orally

58
Q

Fondaprinux

A

synthetic pentasaccharide that binds AT-III, inhibits Xa (not IIa)

59
Q

Toxilizumab

A

anti-IL6 therapy, cholesterol, liver side effects

60
Q

Sulfasalazine

A

combination drug with danger of sulfa allergies and rash

61
Q

Lefulonamide

A

methotrexate-like drug, very teratogenic, inhibits orotic acid dehydrogenase

62
Q

Pyrazinamide

A

URAT1 Stimulator

63
Q

Nicotinate

A

URAT1 Stimulator

64
Q

Organic anions/acids

A

URAT1 Stimulator

65
Q

Salicylate toxicity

A

tinnitus, headache, nausea, dizziness (CN8 irritation)

66
Q

NSAID functions

A

4As: anti-pyretic, analgesic, anti-inflammatory, anti-platelet

67
Q

Lupus Classification Criteria

A

SOAP BRAIN MD: Serositis, Oral ulcers, Arthritis, Photosensitivity, Blood (hematologic), Renal, ANA, Immunologic, Neurological symtpoms, Malar rash, Discoid rash

68
Q

Scleroderma Clinical Presentation

A

CREST: Calcinosis, Raynaud’s Syndrome, Esophageal dysmotility, Sclerodactyly, Telangetacias

69
Q

t(11;18)

A

MALT

70
Q

t(15;17)

A

APL - AML with PML-RARalpha fusion protein

71
Q

t(8;14)

A

Burkitts

72
Q

t(14;18)

A

Follicular lymphoma

73
Q

Fanconi Anemia

A

recessive, x-linked disorder of DNA repair, results in pancytopenia, presetns with congenital abnormalities and increased frequency of MDS and AML

74
Q

Dyskeratosis Congenita

A

disease of poor telomere maintenance, results in chromosome shortening, patient presents with leukoplakia (white sore on tongue) and nail dystrophy

75
Q

Diamond Blackfan Anemia

A

autosomal dominant ribosomopathy (cannot properly assemble ribosome), presents with red cell aplasia, congenital anomalies, increased risk for MDS and AML

76
Q

Top 3 causes of transfusion-related fatality

A
  1. acute hemolytic transfusion reaction
  2. bacterial contamination of platelets (stored at room temp)
  3. TRALI (transfusion-related acute lung injury)
77
Q

p-glycoprotein

A

important resistance mechanism - an ATP-dependent pump that remove antineoplastic drugs from cell - more often successful with naturally-derived agents because protein function is anti-toxin in normal circumstances

78
Q

Ipilimumab

A

monoclonal antibody that binds CTLA4, takes the “brakes” off the immune response, enhances T cell activation

MDTI Memorization (2 decks)

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